Introduction to Bioelectricity Part II

Sabato Santaniello Contributors: Dr. Brown, Dr. Kaputa, Dr. Kumavor, Dr. Shin (UConn BME dept.)

An intuition of “biopotentials”

Source: http://www.youtube.com/watch?v=8IFoUWb8kLQ&playnext=1&list=PL6D9E1BD5963BBF0C&feature=results_main

1 Biopotentials

 An electric voltage that is measured between points in a living cell, tissue, or organism, and which accompanies all biochemical processes

Biopotentials

 An electric voltage that is measured between points in a living cell, tissue, or organism, and which accompanies all

biochemical processes Retina Brain (ganglion cells and  Biopotentials (neurons) photoreceptors) allows organs and muscles to communicate with each other Muscles (muscle fibers) Heart (cardiac cells)

2 Mechanisms behind biopotentials Dendrites (receive signals from other cells) Buttons (form links with other cells) Soma (cell’s life support center and information processing unit) Axon Myelin

Myelin sheath (covers the cell and helps speed the impulses)

Axon

Soma: 0.01 – 0.05 mm (diameter) Axon: 0.001 – 1 m (length) 1 – 25 um (diameter)

Mechanisms behind biopotentials Dendrites (receive signals from other cells) Buttons (form links with other cells) Soma (cell’s life support center and information processing unit) Axon Myelin

Biopotentials are due to the occurrence of one or more electrical impulses (action potentials) at the level of single cells

3 Mechanisms behind biopotentials Dendrites (receive signals from other cells) Buttons (form links with other cells) Soma (cell’s life support center and information processing unit) Axon Myelin

An action potential stems from ions moving across the membrane and travels down from the soma to the axon and buttons

Mechanisms behind biopotentials Dendrites (receive signals from other cells) Buttons (form links with other cells) Soma (cell’s life support center and information processing unit) Axon Myelin

V +++++

+++++

4 Mechanisms behind biopotentials Dendrites (receive signals from other cells) Buttons (form links with other cells) Soma (cell’s life support center and information processing unit) Axon Myelin 50

action voltage (mV) voltage -50 potential V +++++ -100 0 2 4 6 8 10 time (ms) +++++

Features of an action potential voltage

threshold

time  Threshold The net excitation that a excitable cell receives must exceed a minimum intensity to generate an action potential

5 Features of an action potential

all-or-none action potentials voltage

threshold

time  Threshold The net excitation that a excitable cell receives must exceed a minimum intensity to generate an action potential  All-or-none response An excitable cell responds to stimuli of increasing intensity by spiking more, but strength and speed of action potentials remain the same

Features of an action potential

all-or-none action potentials voltage

threshold

6 Ionic concentrations and channels

To understand the mechanisms of an action potential let us first look at what happens across the cell’s membrane

Ionic concentrations and channels

charge separation across the cell membrane

++++++ –––––

Extracellular Intracellular Na+ (sodium) Gradients of ion K+ (potassium) concentration: Cl- (chloride)

7 Ionic concentrations and channels

= − <0

++++++ –––––

 The inside of a cell is always more negative than the outside  The transmembrane voltage at rest is typically between –100Extracellular mV and –60 mVIntracellular Na+ (sodium) Gradients of ion K+ (potassium) concentration: Cl- (chloride)

Ionic concentrations and channels

++++++ –––––

 Potassium (K+) ion concentration is 30-50 times higher inside as compared to outside  Across the membrane there are channels that let pass potassiumExtracellular ions only (ion-specificIntracellular channels) Na+ (sodium) Gradients of ion K+ (potassium) concentration: Cl- (chloride)

8 Ionic concentrations and channels

++++++ –––––

= − Nernst equilibrium ≜ (channels are ion-specific) Extracellular Intracellular

≜ ion valence ≜ universal gas constant ≜ Faraday’s constant ≜ temperature (in ⁰K)

Ionic concentrations and channels

++++++ –––––

= − conductance Nernst equilibrium (reciprocal of ≜ (channels are ion-specific) resistance) Extracellular Intracellular

≜ ion valence ≜ universal gas constant ≜ Faraday’s constant ≜ temperature (in ⁰K)

9 Ionic concentrations and channels

++++++ –––––

= − Nernst equilibrium ≜ (channels are ion-specific) Extracellular Intracellular

−1 −1 = 1 = 8.31 J K mol = 5 mM −1 = 9.65×104 C mol = 37 ⁰C ≅ 310 ⁰K = 155 mM

Ionic concentrations and channels

++++++ –––––

= −

Nernst equilibrium ≅−. (channels are ion-specific) Extracellular Intracellular

−1 −1 = 1 = 8.31 J K mol = 5 mM −1 = 9.65×104 C mol = 37 ⁰C ≅ 310 ⁰K = 155 mM

10 Ionic concentrations and channels

++++++ –––––

 There are other channels across the membrane that let pass only sodium (Na+) or chloride (Cl-) ions  Because ofExtracellular the concentration gradient,Intracellular the flow of Na+ and Cl- ions is opposite to Nathe+ (sodium) flow of K+ ions Gradients of ion K+ (potassium) concentration: Cl- (chloride)

Ionic concentrations and channels

++++++ –––––

= − = −

Extracellular Intracellular = ≅ + = ≅ −

11 Goldman-Hodgkin-Katz equilibrium

++++++ –––––

If nothing perturbs the cell, the sum of the ionic currents will eventually reaches zero (equilibrium). This happens when reaches the value + + = ≝ + +

Goldman-Hodgkin-Katz equilibrium

+ + = ≝ + +

 is called Goldman-Hodgkin-Katz (GHK) equilibrium. It is approximately –85 mV

 , , and are permeability coefficients and account for the ability of the cell’s membrane to be crossed by potassium, sodium, and chloride ions, respectively

12 K-Na active pump

The fact that + + = at GHK equilibrium does not mean that each ionic current is zero

Extracellular Intracellular

K-Na active pump

There is still a flow of Na+, K+, and Cl- ions across the membrane due to concentration gradient

Extracellular Intracellular

13 K-Na active pump

Because the amount of ions inside a cell is finite, this flow would change the concentrations and hence the GHK equilibrium

Extracellular Intracellular

K-Na active pump

The GHK equilibrium remains stable, instead, because there are active pumps across membrane

Extracellular Intracellular

14 K-Na active pump

A pump is a channel that actively pushes K+ ions inside the cell and Na+ ions outside the cell to maintain the original concentration gradient K+ K+

Na+ Na+

Extracellular Intracellular

K-Na active pump

A pump pushes 2 K+ ions inside the cell for every 3 Na+ ions removed from the cell

K+ K+

Na+ Na+

Extracellular Intracellular

15 K-Na active pump

A pump pushes 2 K+ ions inside the cell for every 3 Na+ ions removed from the cell

 Pumps change the electric balance between inside and outside until the concentrations of Na+ and K+ reach the original value again  Pumps consume metabolic energy to perform this task

Note this…

= − = − = −

= ⁄ + = ⁄ + = ⁄ +

16 Note this…

= − = − = −

= + = + = +

Note this…

= − = − = −

outside

pump

pump − − − + + + inside

17 Note this…

The cell’s membrane can be represented as a circuit and can be analyzed with tools we have learned!

outside

pump

pump − − − + + + inside

Note this…

We just need to remember that resistances , , and may vary with the voltage i.e., Ohm’s law is not valid

outside

pump

pump − − − + + + inside

18 Origins of an action potential (AP)

Now we have enough tools to understand how an action potential begins.

Let us first introduce three technical words:

Origins of an action potential (AP)

Now we have enough tools to understand how an action potential begins.

Let us first introduce three technical words:

Because it is more negative inside the cell than outside, the cell’s membrane is said polarized Depolarization: lessening the magnitude of cell polarization by making inside the cell less negative Hyperpolarization: increasing the magnitude of cell polarization by making inside the cell more negative

19 Origins of an action potential (AP)

First, an action potential begins because chemical reactions occur at the dendrites and lead to a sudden increase of the voltage across membrane

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

Origins of an action potential (AP)

During the phase in yellow this cascade of events happens:

depolarization

decrease of

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

20 Origins of an action potential (AP)

During the phase in yellow this cascade of events happens:

depolarization

+ Na inflow decrease of

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

Origins of an action potential (AP)

During the phase in yellow this cascade of events happens:

depolarization

+ Na inflow decrease of

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

21 Origins of an action potential (AP)

During the phase in blue, a saturation has been reached and a new cascade of events starts:

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

Origins of an action potential (AP)

During the phase in blue, a saturation has been reached and a new cascade of events starts: hyperpolarization

K+ outflow

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

22 Origins of an action potential (AP)

During the phase in blue, a saturation has been reached and a new cascade of events starts: hyperpolarization

K+ outflow decrease of

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

Origins of an action potential (AP)

During the phase in blue, a saturation has been reached and a new cascade of events starts: hyperpolarization

K+ outflow decrease of

0 (mV)

threshold -50

-100 0 2 4 6 8 10 12 time (ms)

23 From APs to muscle contraction

 Action potentials are transmitted from one neuron to one another from the brain down the spinal cord until they activate motoneurons

Picture from: Neuroscience. 2nd edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA): Sinauer Associates; 2001

From APs to muscle contraction

 Action potentials are transmitted from one neuron to one another from the brain down the spinal cord until they activate motoneurons  A motoneuron is a neuron that has the soma in the spinal cord and innervates 10 to 2,000 muscle fibers

Picture from: Neuroscience. 2nd edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA): Sinauer Associates; 2001

24 From APs to muscle contraction

Picture from: Neuroscience. 2nd edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA): Sinauer Associates; 2001

From APs to muscle contraction

 A muscle fiber is a cell that converts an action potential in a mechanical contraction

25 From APs to muscle contraction

 A muscle fiber is a cell that converts an action potential in a mechanical contraction

1) Motoneuron 2) Neuro-muscular junction

Electromyogram (EMG)

 EMG measures the electric potential outside the muscle fibers innervated by one or more motoneurons

1) Motoneuron 2) Neuro-muscular junction 3) Muscle fiber 4) Tubular filaments that are contracted because of the action potential

26 Electromyogram (EMG)

 EMG measures the electric potential outside the muscle fibers innervated by one or more motoneurons

1) Motoneuron 2) Neuro-muscular junction 3) Muscle fiber 4) Tubular filaments that are contracted because of the action potential

Electromyogram (EMG)

 EMG measures the electric potential outside the muscle fibers innervated by one or more motoneurons

 Voltage amplitude: 1 – 10 mV  Frequency bandwidth: 20 – 2000 Hz  Electrodes are always connected close to the muscle being measured

 Applications: Muscle function; Neuromuscular disease; Prosthesis